Redox characteristics of MnPorphyrins (metal-centered reduction potential, E1/2) (Batinic-Haberle et al., 2010a), their reactivity toward O2⨪ (as described by rate constant for the catalysis of O2⨪ dismutation, log kcat) (Batinic-Haberle et al., 2010a), and ONOO− (as described by the rate of ONOO− reduction, log kred) (Batinic-Haberle et al., 2010a), and mouse brain concentrations
Dose corrected values are normalized to 1 mg of drug per kg body weight. Reference values are given for native SOD E1/2 (Vance and Miller, 1998) [log kcat(O2⨪)] (Goldstein et al., 2006) and the native ONOO− reductase (its role in vivo is presumed based on the high rate constant), peroxiredoxin [log kred (ONOO−)] (Trujillo et al., 2007). The log POW value is calculated using the equation log Pow=0.96 × nC − 8.82, for MnTE-2-PyP, where nC is a number of carbon atoms in the alkyl chain. The experimentally determined value is provided for MnTnHex-2-PyP.
| Compound | E1/2a | log kcat(O2⨪) | log kred(ONOO−) | log Pow | Brain | Dose Corrected Values |
|---|---|---|---|---|---|---|
| nM | ||||||
| Native Cu-Zn SOD | ∼+300 | ∼9.1 | 3.97b | |||
| Native peroxiredoxin | 8.20 | |||||
| MnTE-2-PyP | +228 | 7.76 | 7.53 | −6.89 | 11c | 1.1 |
| MnTnHex-2-PyP | +314 | 7.48 | 7.11 | −2.76 | 19d | 9.5 |
a E1/2 relates to Mn(III)P/Mn(II)P redox couple.
b Alvarez et al. (2004).
c MnTE-2-PyP mouse brain concentrations 24 h after a single 10 mg/kg i.p. injection (data previously reported in Spasojevic et al., 2008).
d MnTnHex-2-PyP mouse brain concentrations 24 h after a single 2 mg/kg i.p. injection (5-fold lower dose; see Materials and Methods and Results).